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Predictive factors in patients with EGFR mutation-negative non-small cell lung cancer treated with erlotinib.

Ishii H, Azuma K, Yamada K, Kinoshita T, Imamura Y, Hoshino T - Oncol Lett (2014)

Bottom Line: Survival curves were obtained using the Kaplan-Meier method.Multivariate analyses also revealed that pulmonary metastasis independently correlated with PFS and OS times (hazard ratio, 0.39; P=0.0055 and hazard ratio, 0.33; P=0.0022, respectively).Patients with pulmonary metastasis exhibited significantly longer PFS and OS times than those without pulmonary metastasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

ABSTRACT
Factors predicting the efficacy of erlotinib treatment in patients with EGFR mutation-negative non-small-cell lung cancer (NSCLC) have not been well studied. This retrospective study investigates whether patient characteristics, such as site of metastasis, can predict the efficacy of erlotinib treatment in NSCLC patients. In total, 53 EGFR mutation-negative NSCLC patients treated with erlotinib were enrolled, and the associations between clinicopathological characteristics and patient survival were analyzed. The EGFR mutation status was determined using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. Survival curves were obtained using the Kaplan-Meier method. Among the NSCLC patients treated with erlotinib, 27 patients with pulmonary metastasis exhibited significantly longer progression-free survival (PFS) and overall survival (OS) times than those without pulmonary metastasis (median PFS time, 2.9 versus 1.2 months; P=0.0010 and median OS time, 12.4 versus 4.1 months; P=0.0007). Multivariate analyses also revealed that pulmonary metastasis independently correlated with PFS and OS times (hazard ratio, 0.39; P=0.0055 and hazard ratio, 0.33; P=0.0022, respectively). Patients with pulmonary metastasis exhibited significantly longer PFS and OS times than those without pulmonary metastasis. The presence of pulmonary metastasis may be a predictive factor in patients with EGFR mutation-negative NSCLC treated with erlotinib.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves of (A) PFS and (B) OS according to PM. Kaplan-Meier survival curves of (C) PFS and (D) OS according to MPE. PFS, progression-free survival; OS, overall survival; PM, pulmonary metastasis; MPE, malignant pleural effusion.
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f1-ol-08-06-2699: Kaplan-Meier survival curves of (A) PFS and (B) OS according to PM. Kaplan-Meier survival curves of (C) PFS and (D) OS according to MPE. PFS, progression-free survival; OS, overall survival; PM, pulmonary metastasis; MPE, malignant pleural effusion.

Mentions: In total, four patients responded to erlotinib therapy, exhibiting a response rate of 7.5%. All four of these patients also had pulmonary metastasis and malignant pleural effusion with adenocarcinoma. At the time of analysis, the median duration of follow-up was 9.8 months (range, 1.2–31.3 months). The median PFS time for the patients overall was 2.2 months and the median OS time was 6.2 months. Table II shows the patient demographics, excluding metastatic sites, associated with RR, PFS and OS. The patients with improved PS and skin rash following treatment, exhibited longer PFS and OS times than those with poor PS and without skin rash, as indicated in previous studies (PFS, P=0.0002 and P=0.0077; OS, P<0.0001 and P=0.0026, respectively) (18,19). However, other factors were demonstrated to be unrelated to PFS and OS. The median PFS and median OS times for patients according to metastatic sites are shown in Table III. The PFS and OS did not depend on the presence or absence of extrathoracic lymph node and adrenal gland metastasis. In patients with brain, bone and liver metastasis, the median PFS times were shorter than for those patients without these metastases. Furthermore, patients with liver metastasis exhibited a shorter OS time than patients without liver metastasis. The median PFS times in the two groups of patients with and without pulmonary metastasis were 2.9 months (95% CI, 1.9–4.5 months) and 1.2 months (95% CI, 0.8–2.1 months), respectively (P=0.001; Fig. 1A). Although no significant differences were identified between the response rate in patients with and without pulmonary metastasis, the response rate tended to be higher in patients with pulmonary metastasis (response rate, 14.8 vs. 0.0%; P=0.1110). The median duration of OS in the two groups of patients with and without pulmonary metastasis was 12.4 months (95% CI, 5.8–26.2 months) and 4.1 months (95% CI, 2.3–7.6 months), respectively (P=0.0007; Fig. 1B). The response rate in patients with malignant pleural effusion was significantly higher than that of patients without malignant pleural effusion (response rate, 28.6% vs. 0.0%; P=0.0034). However, as shown in Fig. 1C, the median PFS times in the patients with and without malignant pleural effusion were 2.1 and 2.5 months, respectively (P=0.4575). Furthermore, no significant differences were identified in OS between the patients with and without malignant pleural effusion (median OS time, 5.5 months vs. 7.3 months; P=0.9935; Fig. 1D). Of the 13 variables assessed, six were observed to be significantly associated with PFS in univariate analysis: Pulmonary, brain, bone and liver metastasis, plus the onset of skin rash and PS. The multivariate analyses of PFS demonstrated that pulmonary metastasis was an independent and significant predictive factor for PFS (P=0.0055) (Table IV). By contrast, liver metastasis and poor PS were risk factors for an unfavorable PFS following erlotinib therapy (P=0.0279 and P=0.0214, respectively). Additionally, four factors were observed to be significantly associated with OS in the univariate analysis: Pulmonary and liver metastasis plus the onset of skin rash and PS. The presence of pulmonary metastasis was also an independent and significant prognostic factor in the multivariate analysis (P=0.0022).


Predictive factors in patients with EGFR mutation-negative non-small cell lung cancer treated with erlotinib.

Ishii H, Azuma K, Yamada K, Kinoshita T, Imamura Y, Hoshino T - Oncol Lett (2014)

Kaplan-Meier survival curves of (A) PFS and (B) OS according to PM. Kaplan-Meier survival curves of (C) PFS and (D) OS according to MPE. PFS, progression-free survival; OS, overall survival; PM, pulmonary metastasis; MPE, malignant pleural effusion.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214475&req=5

f1-ol-08-06-2699: Kaplan-Meier survival curves of (A) PFS and (B) OS according to PM. Kaplan-Meier survival curves of (C) PFS and (D) OS according to MPE. PFS, progression-free survival; OS, overall survival; PM, pulmonary metastasis; MPE, malignant pleural effusion.
Mentions: In total, four patients responded to erlotinib therapy, exhibiting a response rate of 7.5%. All four of these patients also had pulmonary metastasis and malignant pleural effusion with adenocarcinoma. At the time of analysis, the median duration of follow-up was 9.8 months (range, 1.2–31.3 months). The median PFS time for the patients overall was 2.2 months and the median OS time was 6.2 months. Table II shows the patient demographics, excluding metastatic sites, associated with RR, PFS and OS. The patients with improved PS and skin rash following treatment, exhibited longer PFS and OS times than those with poor PS and without skin rash, as indicated in previous studies (PFS, P=0.0002 and P=0.0077; OS, P<0.0001 and P=0.0026, respectively) (18,19). However, other factors were demonstrated to be unrelated to PFS and OS. The median PFS and median OS times for patients according to metastatic sites are shown in Table III. The PFS and OS did not depend on the presence or absence of extrathoracic lymph node and adrenal gland metastasis. In patients with brain, bone and liver metastasis, the median PFS times were shorter than for those patients without these metastases. Furthermore, patients with liver metastasis exhibited a shorter OS time than patients without liver metastasis. The median PFS times in the two groups of patients with and without pulmonary metastasis were 2.9 months (95% CI, 1.9–4.5 months) and 1.2 months (95% CI, 0.8–2.1 months), respectively (P=0.001; Fig. 1A). Although no significant differences were identified between the response rate in patients with and without pulmonary metastasis, the response rate tended to be higher in patients with pulmonary metastasis (response rate, 14.8 vs. 0.0%; P=0.1110). The median duration of OS in the two groups of patients with and without pulmonary metastasis was 12.4 months (95% CI, 5.8–26.2 months) and 4.1 months (95% CI, 2.3–7.6 months), respectively (P=0.0007; Fig. 1B). The response rate in patients with malignant pleural effusion was significantly higher than that of patients without malignant pleural effusion (response rate, 28.6% vs. 0.0%; P=0.0034). However, as shown in Fig. 1C, the median PFS times in the patients with and without malignant pleural effusion were 2.1 and 2.5 months, respectively (P=0.4575). Furthermore, no significant differences were identified in OS between the patients with and without malignant pleural effusion (median OS time, 5.5 months vs. 7.3 months; P=0.9935; Fig. 1D). Of the 13 variables assessed, six were observed to be significantly associated with PFS in univariate analysis: Pulmonary, brain, bone and liver metastasis, plus the onset of skin rash and PS. The multivariate analyses of PFS demonstrated that pulmonary metastasis was an independent and significant predictive factor for PFS (P=0.0055) (Table IV). By contrast, liver metastasis and poor PS were risk factors for an unfavorable PFS following erlotinib therapy (P=0.0279 and P=0.0214, respectively). Additionally, four factors were observed to be significantly associated with OS in the univariate analysis: Pulmonary and liver metastasis plus the onset of skin rash and PS. The presence of pulmonary metastasis was also an independent and significant prognostic factor in the multivariate analysis (P=0.0022).

Bottom Line: Survival curves were obtained using the Kaplan-Meier method.Multivariate analyses also revealed that pulmonary metastasis independently correlated with PFS and OS times (hazard ratio, 0.39; P=0.0055 and hazard ratio, 0.33; P=0.0022, respectively).Patients with pulmonary metastasis exhibited significantly longer PFS and OS times than those without pulmonary metastasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

ABSTRACT
Factors predicting the efficacy of erlotinib treatment in patients with EGFR mutation-negative non-small-cell lung cancer (NSCLC) have not been well studied. This retrospective study investigates whether patient characteristics, such as site of metastasis, can predict the efficacy of erlotinib treatment in NSCLC patients. In total, 53 EGFR mutation-negative NSCLC patients treated with erlotinib were enrolled, and the associations between clinicopathological characteristics and patient survival were analyzed. The EGFR mutation status was determined using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. Survival curves were obtained using the Kaplan-Meier method. Among the NSCLC patients treated with erlotinib, 27 patients with pulmonary metastasis exhibited significantly longer progression-free survival (PFS) and overall survival (OS) times than those without pulmonary metastasis (median PFS time, 2.9 versus 1.2 months; P=0.0010 and median OS time, 12.4 versus 4.1 months; P=0.0007). Multivariate analyses also revealed that pulmonary metastasis independently correlated with PFS and OS times (hazard ratio, 0.39; P=0.0055 and hazard ratio, 0.33; P=0.0022, respectively). Patients with pulmonary metastasis exhibited significantly longer PFS and OS times than those without pulmonary metastasis. The presence of pulmonary metastasis may be a predictive factor in patients with EGFR mutation-negative NSCLC treated with erlotinib.

No MeSH data available.


Related in: MedlinePlus